Dichloromethane → (E)-ethyl 3-(1-cyclohexyl-6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-3-yl)acrylate

HRID 1628109Notes

Reaction equation

Br[C:2]1[N:3]=[C:4]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[N:5]2[C:10]3[CH:11]=[CH:12][N:13]([S:14]([C:17]4[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=4)(=[O:16])=[O:15])[C:9]=3[N:8]=[CH:7][C:6]=12.C(Cl)Cl.CC1(C)C(C)(C)OB(/[CH:41]=[CH:42]/[C:43]([O:45][CH2:46][CH3:47])=[O:44])O1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH:24]1([C:4]2[N:5]3[C:10]4[CH:11]=[CH:12][N:13]([S:14]([C:17]5[CH:18]=[CH:19][C:20]([CH3:21])=[CH:22][CH:23]=5)(=[O:15])=[O:16])[C:9]=4[N:8]=[CH:7][C:6]3=[C:2](/[CH:41]=[CH:42]/[C:43]([O:45][CH2:46][CH3:47])=[O:44])[N:3]=2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of 3-bromo-1-cyclohexyl-6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine (0.026 g, 0.056 mmol, Example #2, Step E) and PdCl2(dppf).DCM (0.005 g, 0.006 mmol) in THF (1 mL) was added (E)-ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (0.052 g, 0.23 mmol) and Na2CO3 (0.021 g, 0.20 mmol) followed by water (0.25 mL). The mixture was heated to about 65° C. After about 15 h, the mixture was cooled to rt and directly purified by chromatography on silica gel (12 g) eluting with 20 to 80% EtOAc:DCM (1:1) in heptane to provide (E)-ethyl 3-(1-cyclohexyl-6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-3-yl)acrylate (0.045 g, 70%): LC/MS (Table 2, Method a) Rt=3.15 min; MS m/z: 493 (M+H)+.

Workup

temperaturethe mixture was cooled to rt
customdirectly purified by chromatography on silica gel (12 g)
washeluting with 20 to 80% EtOAc:DCM (1:1) in heptane

Sources & evidence

ORD record: ord-c342064f918b4780ae6663da075c858b
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785639B2

Reaction notes

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